Treatment of Early Age Mania (TEAM)

描述(申请人提供)：儿童双相情感障碍(BP-I)是一种慢性疾病，严重损害家庭、学校和同伴功能，并与高精神病、混合性躁狂、极端快速循环和自杀有关。即使是聪明的孩子也会在学校里成绩不及格，而且大多数人都需要大量的药物治疗。鉴于承认儿童BP存在的新鲜事，目前还缺乏治疗方面的知识，包括对成人BP显示有效的药物是否会对儿童产生类似的效果。关于治疗，两个更紧迫的问题是(1)首先使用哪类药物(锂、丙戊酸盐、非典型抗精神病药物)和(2)如果第一种药物无效，应补充或改用哪种药物。为了研究这些研究问题，团队项目于两年前启动，作为一项复杂的、多地点、多层次、均衡分层、适应性策略设计，研究了540名患有6-15岁儿童BP-I(躁狂期或混合期)的受试者。在这个范例中，受试者被随机分成三层，其中包括第一层，对于那些没有服用研究药物的人。第二层是一种附加策略，适用于那些对一种研究药物部分有效的人。第三层是一种交叉缩减策略，适用于那些未能通过一项研究药物治疗的人。此外，在第一层中部分或反应较差的受试者被重新随机分配到其他两层。由于这种设计的新颖性和成本，NIMH要求团队从两年的试点开始，条件是如果两年的试点证明是可行的，将鼓励调查人员申请额外的四年资金来完成研究。在编写本报告时(2004年6月7日提交日期为5/27)，共有107名随机受试者，超过了计划的招聘率。此外，所有三个层面都在填补。因此，可行性已经确立。作为一项大型合作协议，这项研究由NIMH数据和安全监测委员会(DSMB)每季度监测一次。在撰写本文时进行的五次DSMB审计中，团队在数据管理、质量控制和安全方面获得了突出的赞誉。这项合作协议的结构是一个协调站点(华盛顿大学圣路易斯分校，PI：B.Geller)和五个数据收集站点(儿童国家医疗中心，PI：P.Joshi；约翰霍普金斯大学医疗机构，PI：J.Walkup；匹兹堡大学，PI：D.Axelson；UT医疗分支，加尔维斯顿，PI：K.Dineen Wagner；华盛顿大学在圣路易斯，PI：J.Luby)。本·维蒂洛博士是NIMH的科学合作者。首席研究统计师萨蒂什·莱恩加博士被分包到位于圣路易斯的华盛顿大学的协调地点，菲利普·拉沃里博士是统计分析的主要顾问。

DESCRIPTION (provided by applicant): Childhood bipolar disorder (BP-I) is a chronic illness that seriously impairs home, school and peer functioning and is associated with high rates of psychosis, mixed mania, ultradian rapid cycling and suicidality. Even bright children get failing grades at school and most require a myriad of medications. Given the newness of recognizing the existence of child BP, there is as yet scant knowledge of treatment, including whether medications that have shown effectiveness in adult BP will have similar effects in children. Regarding treatment, two of the more pressing issues have been (1) which class of drug to use first (lithium, valproate, atypical neuroleptics) and (2) which drug to add-on or switch to if the first drug fails. To investigate these research questions, the TEAM project was initiated two years ago as a complex, multi-site, multi-strata, equipoise stratification, adaptive strategy design to study 540 subjects with child BP-I (manic or mixed phase), aged 6-15. In this paradigm, subjects are randomized within three strata that include Stratum One for those on no study medications. Stratum Two is an add-on strategy for those who are partial responders to one study drug. Stratum Three is a cross-taper strategy for those who have failed one study medication. Also, subjects who are partial or poor responders in Stratum One are re-randomized to the other two strata. Due to the novelty and cost of this design, NIMH requested that TEAM begin as a two year pilot, with the proviso that if the two year pilot demonstrated feasibility, the investigators would be encouraged to apply for an additional four years of funding to complete the study. At the time of this writing (5/27/04 for a 6/7/04 submission date), there are 107 randomized subjects, which exceeds the planned recruitment rate. Furthermore, all three strata are being filled. Therefore, feasibility has been established. As a large cooperative agreement, this study is monitored on a quarterly basis by the NIMH Data and Safety Monitoring Board (DSMB). At the five DSMB audits conducted at the time of this writing, TEAM has received outstanding praise for data management, quality control, and safety. The structure of this cooperative agreement is one coordinating site (Washington U in St. Louis, PI: B. Geller) and five data collection sites (Children's National Medical Center, PI: P. Joshi; Johns Hopkins Medical Institutions, PI: J. Walkup; U Pittsburgh, PI: D. Axelson; UT Medical Branch, Galveston, PI: K. Dineen Wagner; Washington U in St. Louis, PI: J. Luby). Dr. Ben Vitiello is the NIMH scientific collaborator. The chief study statistician, Dr. Satish lyengar is subcontracted to the coordinating site at Washington U in St. Louis and Dr. Philip Lavori is a major consultant for statistical analyses.